Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients
Hajeer A. H, Dababneh A, Makki R. F, Thomson W, Poulton K, Gonzalez-Gay M. A, Garcia-Porrua C, Mattey D. L, Ollier WER
Tissue Antigens. 2000;55, 4:319-25.
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The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. RA patients (n=179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n=145) were recruited. RA susceptibility in this population was predominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04. The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner. Logistic regression analyses revealed that the TNF microsatellite markers TNFc1 and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF c1 allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals. TNFc1 and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFc1) polymorphism seemingly associated with low TNFalpha production, is a risk factor for RA.
Adult; Arthritis, Rheumatoid/*genetics/*immunology; Female; Genetic Predisposition to Disease; HLA-DR Antigens/*genetics; Haplotypes; Human; Logistic Models; Male; Microsatellite Repeats; Middle Age; Phenotype; Polymorphism (Genetics); Severity of Illness Index; Spain; Tumor Necrosis Factor/*genetics